In eukaryotes, mRNAs encoding secretory and integral membrane proteins are selectively partitioned to the endoplasmic reticulum (ER) via the signal recognition particle (SRP) pathway. However, early studies suggest that mRNA binds to the ER in the absence of ribosomes. Furthermore, recent studies demonstrate that mRNAs encoding cytosolic proteins can be translated on and, in some cases, highly partitioned to ER bound polysomes. Because these mRNAs do not encode for signal sequences, it is unlikely that the SRP pathway functions in their trafficking to the ER. Thus, we hypothesize that a novel, ER-directed mRNA localization pathway exists that contributes to the partitioning processes governing mRNA distribution in the cell. In the following studies we will define the mechanism of mRNA association with the ER and identify cis and trans acting factors that contribute to ER-directed mRNA localization. Our proposed focus on the mechanism of ER-directed mRNA localization is expected to yield the identification of the molecular machinery functioning in this previously unappreciated and likely fundamental mRNA partitioning pathway.